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AGTR1基因A1166C多态性和CYP2C9∗3基因多态性与缬沙坦降压效果的关联

Association of AGTR1 A1166C and CYP2C9∗3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan.

作者信息

Liu Yi, Kong Xiaomu, Jiang Yongwei, Zhao Meimei, Gao Peng, Cong Xiao, Cao Yongtong, Ma Liang

机构信息

Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China.

出版信息

Int J Hypertens. 2022 Mar 19;2022:7677252. doi: 10.1155/2022/7677252. eCollection 2022.

Abstract

BACKGROUND

The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor () gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 () gene polymorphism (∗3).

METHODS

281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the and gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group ( = 144, SBP/DBP <140/90 mmHg) and poorly controlled group ( = 137, SBP/DBP ≥140/90 mmHg).

RESULTS

Older age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of A1166C were detected in the well-controlled than the poorly controlled patients ( = 0.005 and  = 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199-6.705,  = 0.018). No significant difference was observed in the allele or genotype distribution of ∗3 polymorphism between well-controlled and poorly controlled patients.

CONCLUSIONS

The current data suggested that the A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.

摘要

背景

使用血管紧张素II受体阻滞剂(ARB)进行降压治疗的差异可能归因于涉及药物靶向受体和药物代谢的基因多态性。本研究旨在调查ARB药物缬沙坦的降压效果是否与血管紧张素II 1型受体(AT1R)基因多态性(A1166C)和细胞色素P450酶2C9(CYP2C9)基因多态性(*3)相关。

方法

本回顾性研究纳入了过去一个月接受缬沙坦单药治疗的281例高血压患者。采用聚合酶链反应-熔解曲线分析对AT1R和CYP2C9基因多态性进行基因分型。根据就诊时的收缩压(SBP)和舒张压(DBP),将患者分为血压控制良好组(n = 144,SBP/DBP <140/90 mmHg)和血压控制不佳组(n = 137,SBP/DBP≥140/90 mmHg)。

结果

与血压控制不佳组相比,血压控制良好组患者年龄更大、饮酒史减少、轻度至中度高血压比例更高、丙氨酸转氨酶水平更低、高密度脂蛋白胆固醇水平更高。与血压控制不佳的患者相比,血压控制良好的患者中检测到AT1R A1166C的C等位基因和AC + CC基因型频率更高(P = 0.005和P = 0.006)。在调整人口统计学和环境因素后,与AA基因型相比,AT1R A1166C的CC + AC基因型与缬沙坦治疗更好的高血压控制显著相关(优势比:2.836,95%置信区间:1.199 - 6.705,P = 0.018)。血压控制良好和不佳的患者之间,CYP2C9 *3多态性的等位基因或基因型分布未观察到显著差异。

结论

目前的数据表明,AT1R A1166C多态性可能与缬沙坦的降压效果相关,AC和CC基因型携带者可能对缬沙坦治疗有更好的降压疗效反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f46/8957473/3d74c81df6f2/ijhy2022-7677252.001.jpg

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